Compositions and methods using P-anisaldehyde

ABSTRACT

Compositions contain a therapeutically effective amount of p-anisaldehyde for at least one of provoking the swallowing reflex of dysphagic patients, decreasing appetite by delaying gastric emptying, reducing body weight gain, or reducing gylcemia by improving insulin sensitivity, or improving mood, memory or cognition. Methods are provided that include administering such compositions.

CROSS REFERENCE TO RELATED APPLICATIONS

The present application is a National Stage of International ApplicationNo. PCT/EP2014/065472, filed on Jul. 18, 2014, which claims priority toU.S. Provisional Application Ser. No. 61/857,060, filed Jul. 22, 2013,the entire contents of which are being incorporated herein by reference.

BACKGROUND

The present disclosure generally relates to compositions comprising anaturally-occurring compound found in some spices. More specifically,the present disclosure relates to compositions comprising p-anisaldehydeand further relates to methods comprising administering suchcompositions.

Dysphagia is a condition typified by a decreased ability to swallow. Thenormal swallow involves three distinct phases which are interdependentand well coordinated: the oral, the pharyngeal, and the esophagealphases. In the oral phase, which is under voluntary control, food thathas been chewed and mixed with saliva is formed into a bolus fordelivery by voluntary tongue movements to the back of the mouth, intothe pharynx. The pharyngeal phase is involuntary and is triggered by thefood/liquid bolus passing through the faucial pillars into the pharynx.Contraction of the three constrictors of the pharynx propels the bolustowards the upper oesophageal sphincter. Simultaneously, the soft palatecloses the nasopharynx. The larynx moves upwards to prevent food orliquid passing into the airway, which is aided by the backward tilt ofthe epiglottis and closure of the vocal folds. The oesophageal phase isalso involuntary and starts with the relaxation of the upper oesophagealsphincter followed by peristalsis, which pushes the bolus down to thestomach.

Esophageal dysphagia affects a large number of individuals of all ages,but is generally treatable with medications and is considered a lessserious form of dysphagia. Oral pharyngeal dysphagia, on the other hand,is a very serious condition and is generally not treatable withmedication. Oral pharyngeal dysphagia also affects individuals of allages, but is more prevalent in older individuals. Worldwide, oralpharyngeal dysphagia affects approximately 22 million people over theage of 50.

The consequences of untreated or poorly managed oral pharyngealdysphagia can be severe, including dehydration, malnutrition, airwayobstruction with solid foods (choking), and airway aspiration of liquidsand semi-solid foods, promoting aspiration pneumonia and/or pneumonitis.Severe oral pharyngeal dysphagia may require nutrition to be supplied bytube feeding. Mild to moderate oral pharyngeal dysphagia requires thetexture of foods to be modified in order to minimize the likelihood ofchoking or aspiration.

Improving an individual's ability and efficiency to swallow improves theindividual's safety through reduced risk of pulmonary aspiration. Anefficient swallow may permit greater independence from feedingassistance and/or reduced length of time spent in feeding-assistanceduring meal consumption. Efficient swallow also reduces the viscosity ofliquids required for safety (e.g., pudding, honey and nectar thicknessproducts) and may also limit the use of texture-modified foods. All ofthese previously described factors are aimed at improving anindividual's quality of life.

Research on the molecular mechanisms underlying pungent sensationsrevealed the existence of two cation channels, TRPV1 (transient receptorpotential V1) and TRPA1 (transient receptor potential A1) that areexpressed in the somatosensory fibers innervating the oral cavity. TRPV1is the receptor for heat and burning sensations such as capsaicin, thehot molecule in red hot chili peppers. TRPA1 responds to cold andpungent compounds such as allyl isothiocyanate (mustard oil) andcinnamaldehyde (cinnamon). At moderated concentrations, TRPA1 agonistsexhibit a pleasant tingling sensation.

Although oral administration of capsaicin has been shown to promote aswallow reflex, capsaicin is a particularly pungent and toxic compound.Physiological effects associated with oral administration of capsaicininclude a burning sensation of heat from the mid-tongue to the throat,shortness of breath, fainting, nausea, and spontaneous vomiting. Mustardoil is similarly pungent, and cinnamaldehyde is tingling. As a result,only small quantities of capsaicin, mustard oil or cinnamaldehyde may beadministered without causing discomfort to the individual. Food productscontaining capsaicin, mustard oil or cinnamaldehyde are frequently notaccepted by the consumer as providing a very unpleasant mouth feeling.In particular, both the tingling and burning effect are considered to bevery unsavory affecting the consumption of the food product.

Another condition adversely affecting some individuals is that theirbody tissues do not respond properly to insulin. Insulin receptors inthe tissues cease to function adequately and gluco-dependant cells failto recognize the presence of insulin. As a result, the pancreas needs tosecrete more insulin to help glucose enter these cells. The pancreastries to keep up with this increased demand for insulin by producingmore. This phenomenon is called insulin resistance (also known as lowinsulin sensitivity). Many people with insulin resistance have highlevels of both glucose and insulin circulating in their blood at thesame time. Eventually, the pancreas fails to keep up with the body'sneed for insulin, leading to Type II diabetes.

Insulin resistance and Type II diabetes are associated to increased riskof heart attacks, strokes, amputation, diabetic retinopathy, and kidneyfailure. For extreme cases, circulation of limbs is affected,potentially requiring amputation. Loss of hearing, eyesight, andcognitive ability has also been linked to these conditions

Management of insulin resistance in children and adults is essentiallybased on dietary and lifestyle changes, including healthier dietaryhabits and increased exercise. These practices can be very efficient inimproving insulin sensitivity and in slowing the progression of thedisease, but they are difficult to apply and actually not followed bymost patients. Type II diabetes can be treated with drugs promotinginsulin sensitivity, but their efficacy in reducing the rate ofprogression of the disease is quite low. Insulin treatment is requiredduring the most advanced phases of the disease.

Products containing n−3 polyunsaturated fatty acids, fibers,oligosaccharides and even probiotics have been proposed as nutritionalsolutions to improve insulin sensitivity and to reduce insulinresistance. However, the efficacy of these nutritional interventions isquite marginal and even controversial, with studies showing no or evendeleterious effects.

Yet another condition adversely affecting some individuals is obesity.The prevalence of obesity has increased worldwide to epidemicproportion. Approximately 1 billion of people worldwide are overweightor obese, conditions that increase mortality, mobility and economicalcosts. Obesity develops when energy intake is greater than energyexpenditure, the excess energy stored mainly as fat in adipose tissue.Body weight loss and prevention of weight gain can be achieved byreducing energy intake or bioavailability, increasing energy expenditureand/or reducing storage as fat. However, overweight subjects or subjectsat risk of becoming overweight often need nutritional assistance forbetter managing their body weight, e.g. through increasing satietyand/or reducing body weight gain.

Yet another condition adversely affecting some individuals is impairedneurotransmission, for example low levels of neurotransmitters such asepinephrine. Impaired neurotransmission is connected to mood disorderssuch as depression, anxiety disorders, and increased susceptibility tostress, and also connected to cognitive dysfunction.

Carbohydrate-rich foods are known for providing important metabolic fuelfor physical performance, but their effects on mood and cognitiveperformance are not very clear. However, irritability and aggression areinfluenced by individual differences in insulin release, the frequencythat meals are eaten, and the effect of these meals on blood glucosevalues. Benton, “Carbohydrate ingestion, blood glucose and mood,”Neuroscience and Biobehavioral Reviews, 26:293-308 (2002). Furthermore,the ability to control the levels of blood glucose is related to bothmood and cognition. For example, in a study in which participants weregiven an oral glucose tolerance test and cognitive tests, the older agegroup showed that those with poorer glucose tolerance forgot more wordsand had slower decision times; and, in those participants with poorglucose tolerance, a tendency for blood glucose to fall below baselinevalues was associated with better mood and faster working memory. Youngand Benton, “The nature of the control of blood glucose in those withpoorer glucose tolerance influences mood and cognition,” Metab. BrainDis. (Mar. 26, 2014).

SUMMARY

The present inventors surprisingly and unexpectedly found thatp-anisaldehyde is an agonist of the cation channels TRPA1 and TRPV1.Without wishing to be bound by theory, the present inventors believethat activation of TRPA1 and TRPV1 is effective to 1) help to provokethe swallowing reflex of dysphagic patients, 2) decrease appetite bydelaying gastric emptying, 3) reduce body weight gain, and 4) reducegylcemia by improving insulin sensitivity or glucose tolerance 5)improve mood, memory or cognition. P-anisaldehyde is described as havingsweet powdery, vanilla creamy, spice anise, nutty, cherry pit andalmond-like nuances (Fenaroli's Handbook of Flavor Ingredients, sixthedition), making it more pleasant compared to other TRPA1 and TRPV1agonists.

Accordingly, in a general embodiment, the present disclosure provides amethod of treating dysphagia. The method comprises administering to anindividual having the dysphagia a composition comprising atherapeutically effective amount of p-anisaldehyde.

In a related embodiment, the dysphagia is oral pharyngeal dysphagia.

In a related embodiment, the composition is a thickened beverage.

In a related embodiment, the therapeutically effective amount ofp-anisaldehyde provokes a swallowing reflex.

In a related embodiment, the p-anisaldehyde is selected from the groupconsisting of isolated p-anisaldehyde and synthetic p-anisaldehyde.

In another embodiment, a method of decreasing appetite is provided. Themethod comprises administering to an individual in need thereof acomposition comprising p-anisaldehyde in an amount therapeuticallyeffective for delaying gastric emptying.

In a related embodiment, the individual has a condition selected fromoverweight, obesity, a risk of overweight, a risk of obesity, andcombinations thereof.

In another embodiment, a method of reducing body weight gain isprovided. The method comprises administering to an individual in needthereof a composition comprising a therapeutically effective amount ofp-anisaldehyde.

In a related embodiment, the individual has a condition selected fromoverweight, obesity, a risk of overweight, a risk of obesity, andcombinations thereof.

In another embodiment, a method of reducing glycemia is provided. Themethod comprises administering to an individual in need thereof acomposition comprising p-anisaldehyde in an amount therapeuticallyeffective for improving insulin sensitivity or glucose tolerance, moodor memory.

In a related embodiment, the individual is selected from the groupconsisting of an infant born preterm, an infant experiencingintrauterine growth restriction, a pregnant woman suffering fromgestational diabetes, a human suffering from insulin resistance, and ahuman suffering from type II diabetes.

In another embodiment, a composition is provided. The compositioncomprises an amount of p-anisaldehyde that is therapeutically effectivefor at least one of provoking the swallowing reflex of dysphagicpatients, decreasing appetite by delaying gastric emptying, reducingbody weight gain, or reducing glycemia by improving insulin sensitivityor glucose tolerance, or improving mood or memory or cognition.

In a related embodiment, the composition is a food product. The foodproduct can comprise a component selected from the group consisting ofprotein, carbohydrate, fat and combinations thereof.

In another embodiment, the present disclosure provides a method forimproving one or more of cognitive performance, cognition, mood, ormemory comprising administering to an individual in need thereof acomposition comprising a therapeutically effective amount ofp-anisaldehyde.

In an embodiment, the individual has a condition selected from the groupconsisting of cognitive decline, mild cognitive impairment, dementia, amood disorder, memory loss, and combinations thereof.

In another embodiment, a method of making a nutritional composition isprovided. The method comprises incorporating into the nutritionalcomposition an amount of p-anisaldehyde that is therapeuticallyeffective for at least one of provoking the swallowing reflex ofdysphagic patients, decreasing appetite by delaying gastric emptying,reducing body weight gain, or reducing glycemia by improving insulinsensitivity or glucose tolerance, or improving mood or memory.

An advantage of the present disclosure is to use a TRPA1 and TRPV1agonist that is more pleasantly consumed relative to other TRPA1 andTRPV1 agonists.

Another advantage of the present disclosure is to use p-anisaldehyde totrigger the swallowing reflex of a dysphagic patient.

Still another advantage of the present disclosure is use anaturally-occurring compound that can be found in spices to decreaseappetite by delaying gastric emptying.

Yet another advantage of the present disclosure is to use anaturally-occurring compound that can be found in spices to reduce bodyweight gain.

An additional advantage of the present disclosure is to use anaturally-occurring compound that can be found in spices to reducegylcemia by improving insulin sensitivity or glucose tolerance

Another advantage of the present disclosure is to treat dysphagia withtolerable side effects or no side effects.

Still another advantage of the present disclosure is to promote safeswallowing of a food bolus.

Still another advantage of the present disclosure is to improve at leastone of mood, memory or cognition.

Still another advantage of the present disclosure is to improve at leastone of mood, memory or cognition with a compound that can be easily andsafely used in food products.

An additional advantage of the present disclosure is to improve at leastone of mood, memory or cognition with a naturally-occurring compoundthat can be found in spices.

Another advantage of the present disclosure is to improve at least oneof mood, memory or cognition with tolerable side effects or no sideeffects.

Yet another advantage of the present disclosure is to improve at leastone of mood, memory or cognition with a compound that has increasedacceptability, reduced pungency, and improved tolerance in thegastrointestinal tract relative to capsaicin.

Additional features and advantages are described herein, and will beapparent from, the following Detailed Description and the Figures.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 shows the chemical structure of p-anisaldehyde.

FIG. 2 shows the chemical structure of cinnamaldehyde.

FIG. 3 shows a chart of body weight gain in mice with chronic ingestionof cinnamaldehyde or control.

FIG. 4 shows a chart of insulin sensitivity in mice with chronicingestion of cinnamaldehyde or control.

FIG. 5 shows a chart of short term food intake gain after a singlecinnamaldehyde or control ingestion in mice.

FIG. 6 shows a chart of gastric emptying after a single cinnamaldehydeor control ingestion in mice.

FIG. 7 shows the in vitro effect of p-anisaldehyde on cell expression ofTRP channels.

DETAILED DESCRIPTION

All percentages expressed herein are by weight of the total weight ofthe composition unless expressed otherwise. When reference is made tothe pH, values correspond to pH measured at 25° C. with standardequipment. As used in this disclosure and the appended claims, thesingular forms “a,” “an” and “the” include plural referents unless thecontext clearly dictates otherwise. As used herein, “about” isunderstood to refer to numbers in a range of numerals. Moreover, allnumerical ranges herein should be understood to include all integers,whole or fractions, within the range.

As used herein, “comprising,” “including” and “containing” are inclusiveor open-ended terms that do not exclude additional, unrecited elementsor method steps. However, the beverages provided by the presentdisclosure may lack any element that is not specifically disclosedherein. Thus, any embodiment defined herein using the term “comprising”also includes embodiments “consisting essentially of” and “consistingof” the disclosed components.

“Prevention” includes reduction of risk and/or severity of a disorder.The terms “treatment,” “treat” and “to alleviate” include bothprophylactic or preventive treatment (that prevent and/or slow thedevelopment of a targeted pathologic condition or disorder) andcurative, therapeutic or disease-modifying treatment, includingtherapeutic measures that cure, slow down, lessen symptoms of, and/orhalt progression of a diagnosed pathologic condition or disorder; andtreatment of patients at risk of contracting a disease or suspected tohave contracted a disease, as well as patients who are ill or have beendiagnosed as suffering from a disease or medical condition. The termdoes not necessarily imply that a subject is treated until totalrecovery. The terms “treatment” and “treat” also refer to themaintenance and/or promotion of health in an individual not sufferingfrom a disease but who may be susceptible to the development of anunhealthy condition. The terms “treatment,” “treat” and “to alleviate”are also intended to include the potentiation or otherwise enhancementof one or more primary prophylactic or therapeutic measures. The terms“treatment,” “treat” and “alleviate” are further intended to include thedietary management of a disease or condition or the dietary managementfor prophylaxis or prevention a disease or condition. A treatment can bepatient- or doctor-related.

As used herein, a “therapeutically effective amount” is an amount thatprevents a deficiency, treats a disease or medical condition in anindividual or, more generally, reduces symptoms, manages progression ofthe diseases, or provides a nutritional, physiological, or medicalbenefit to the individual.

“Animal” includes, but is not limited to, mammals, which includes but isnot limited to, rodents, aquatic mammals, domestic animals such as dogsand cats, farm animals such as sheep, pigs, cows and horses, and humans.Where “animal,” “mammal” or a plural thereof is used, these terms alsoapply to any animal that is capable of the effect exhibited or intendedto be exhibited by the context of the passage. As used herein, the term“patient” is understood to include an animal, especially a mammal, andmore especially a human that is receiving or intended to receivetreatment, as treatment is herein defined. While the terms “individual”and “patient” are often used herein to refer to a human, the presentdisclosure is not so limited. Accordingly, the terms “individual” and“patient” refer to any animal, mammal or human, having or at risk for amedical condition that can benefit from the treatment.

“Food product” and “food composition,” as used herein, are understood toinclude any number of optional additional ingredients, includingconventional food additives, for example one or more proteins,carbohydrates, fats, acidulants, thickeners, buffers or agents for pHadjustment, chelating agents, colorants, emulsifiers, excipients, flavoragents, minerals, osmotic agents, a pharmaceutically acceptable carrier,preservatives, stabilizers, sugars, sweeteners, texturizers and/orvitamins. The optional ingredients can be added in any suitable amount.

As noted above, the present inventors surprisingly and unexpectedlyfound that p-anisaldehyde (chemical structure shown in FIG. 1) is anagonist of the cation channels TRPA1 and TRPV1. FIG. 7 showsexperimental data demonstrating that p-anisaldehyde activates TRPA1 andTRPV1. P-anisaldehyde activated TRPA1 with an EC-50 of about 100 μM(circles) and TRPV1 with an EC 50 of about 500 μM (squares), and noactivation was observed on hTRPM8 (upward pointing triangles) and“empty” cells (downward pointing triangles).

The present inventors tested cinnamaldehyde (chemical structure shown inFIG. 2), a known TRPA1 agonist, in mouse models. Cinnamaldehyde is aα,β-unsaturated aldehyde that activates TRPA1, but not TRPV1 or TRPM8,with an EC50 of approximately 60 μM. Like mustard oil, cinnamaldehydeinteracts with TRPA1 in a covalent manner.

As shown in FIG. 3, mice chronically fed a high fat diet containing 0.2wt % cinnamaldehyde gained less weight than mice fed the same high fatdiet without cinnamaldehyde. As shown in FIG. 4, mice chronically fed ahigh fat diet containing 0.2 wt % cinnamaldehyde had improved insulinsensitivity relative to mice fed the same high fat diet withoutcinnamaldehyde. As shown in FIG. 5, mice fed a single dose ofcinnamaldehyde had a reduction in short term food intake after theadministration relative to mice fed a sham gavage. As shown in FIG. 6,mice fed a single dose of cinnamaldehyde had delayed gastric emptyingafter the administration relative to mice fed a sham gavage.

Due to the unexpected discovery that p-anisaldehyde is also an agonistof the cation channels TRPA1 and TRPV1, the present inventors believethat p-anisaldehyde can activate TRPA1 similarly to cinnamaldehyde, butwithout the tingling sensation, and activate TRPV1 similarly tocapsaicin, but without the burning sensation, to 1) help to provoke theswallowing reflex of dysphagic patients, 2) decrease appetite bydelaying gastric emptying, 3) reduce body weight gain, and 4) reducegylcemia by improving insulin sensitivity. Accordingly, the presentdisclosure provides a composition comprising a therapeutically effectiveamount of p-anisaldehyde for provoking the swallowing reflex of adysphagic patient, decreasing appetite by delaying gastric emptying,reducing body weight gain, and/or reducing gylcemia by improving insulinsensitivity or glucose tolerance 5) improve mood, memory or cognition.In an embodiment, the p-anisaldehyde can be an isolated compound, suchas p-anisaldehyde isolated from spices, such as vanilla; anise, such asstar anise; fennel; cranberry; cinnamon; basil; and extracts thereof.Alternatively or additionally, the p-anisaldehyde can be isolated fromsome essential oils. In an embodiment, the p-anisaldehyde can besynthetic p-anisaldehyde.

In an embodiment, dysphagia is treated by administering to an individualhaving the dysphagia the composition comprising a therapeuticallyeffective amount of p-anisaldehyde. The dysphagia can be oral pharyngealdysphagia and can be a consequence of at least one of surgery for oralcancer, surgery for throat cancer, a stroke, a brain injury, or aprogressive neuromuscular disease, such as Parkinson's disease.

In another embodiment, the composition comprising a therapeuticallyeffective amount of p-anisaldehyde is administered to an infant (a childunder the age of 12 months) born preterm and/or experiencingintrauterine growth restriction (IUGR), a pregnant woman suffering fromgestational diabetes; or a child, an adolescent, or an adult sufferingfrom insulin resistance and/or type II diabetes, such as an animal suchas a human. The composition can reduce glycemia by improving insulinsensitivity or glucose tolerance in the subject.

In yet another embodiment, the composition is administered to anoverweight or obese subject or to a subject at risk for becomingoverweight or obese. “Overweight” is defined for an adult human ashaving a BMI between 25 and 30. Thereby, BMI (body mass index) means theratio of weight in kilograms divided by the height in meters squared; orthe ratio of weight in pounds divided by the height in inches squared,multiplied by 703. “Obesity” is a condition in which the natural energyreserve, stored in the fatty tissue of animals, in particular humans andother mammals, is increased to a point where it is associated withcertain health conditions or increased mortality. “Obese” is defined fora human as having a BMI greater than 30. The composition can decreaseappetite by delaying gastric emptying and/or reduce body weight gain inthe subject. In an embodiment, the subject is a non-overweight and/ornon-obese individual avoiding weight gain.

As noted above, there is a direct link between glucose tolerance andmood, memory and cognition. For example, in a study in whichparticipants were given an oral glucose tolerance test and cognitivetests, the older age group showed that those with poorer glucosetolerance forgot more words and had slower decision times; and, in thoseparticipants with poor glucose tolerance, a tendency for blood glucoseto fall below baseline values was associated with better mood and fasterworking memory. See, e.g., Young and Benton (2014). Therefore, withoutbeing bound by theory, the inventors believe that p-anisaldehydeenhances insulin sensitivity and/or glucose tolerance and can therebyimprove one or more of mood, memory or cognition.

Accordingly, in an embodiment, the composition comprising p-anisaldehydecan be administered in a method of improving one or more of cognitiveperformance, cognition, mood or memory in an individual in need thereof.The composition can treat or prevent one or more of cognitive decline,mild cognitive impairment, dementia, a mood disorder, or memory loss inan individual having one or more of these conditions. The compositioncan be administered at least once a day for at least one week,preferably at least one month, and more preferably at least one year.The composition can be administered to an infant (a child under the ageof twelve months), a child (up to twelve years of age), an adolescent(twelve to eighteen years of age), an adult (over eighteen years ofage), or an elderly individual (past the first two thirds of the averageexpected lifespan in its country of origin, preferably past the firstthree quarters of the average expected lifespan in its country oforigin; an elderly human is a person with a chronological age of 65years or older).

Cognitive performance may be expressed as ability and speed of learning,ability and speed of solving intellectual problems, ability to form andrecall memories, reaction time, and the like. Cognition is understood asmental processes such as comprehension, inference, decision-making,planning, learning, memory, association, concept formation, language,attention, perception, action, problem solving and mental images.Cognitive decline may manifest as reduced memory; forgetfulness; word orname-finding problems; and/or decline in memory, concentration, abilityto plan or organize, ability to perform complex tasks, and/or cognitiveperformance; and may result from age, stress, disease, or other grounds.Cognitive impairment may manifest in one or more of short-term memoryloss, diminished capacity to learn, diminished rate of learning, ordiminished attention.

The term “mood” refers to a state or quality of feeling (an emotionalstate) at a particular time. Moods differ from simple emotions in thatthey are less specific, less intense, and less likely to be triggered bya particular stimulus or event. Moods generally have either a positiveor negative valence. An improved mood may comprise one or more of adecreased anxiety level, a decreased stress level, an increasedperceived energy level, or a more positive emotional state.

The composition is in an administrable form which is preferably selectedfrom the group consisting of pharmaceutical formulations, nutritionalformulations, dietary supplements, functional food and beverageproducts, and combinations thereof. The present disclosure provides amethod of making a nutritional composition that includes incorporating atherapeutically effective amount of p-anisaldehyde into the nutritionalcomposition. The p-anisaldehyde incorporated into the nutritionalcomposition can be in the form of isolated p-anisaldehyde, a spice thatcontains p-anisaldehyde, and/or an extract of a spice that containsp-anisaldehyde.

With respect to dysphagia, a preferred embodiment of the compositionadministers a therapeutically effective amount of p-anisaldehyde as anutritional supplement, such as a nutrient-dense beverage. In anotherpreferred embodiment for treatment of dysphagia, the therapeuticallyeffective amount of p-anisaldehyde is administered in a hydrationsupplement. Such supplements may be in the form of a thickened liquid.In yet another preferred embodiment for treatment of dysphagia, thetherapeutically effective amount of p-anisaldehyde is administered in atexture-modified food.

In an embodiment, the composition includes a prebiotic. The prebioticmay preferably be selected from the group consisting of acacia gum,alpha glucan, arabinogalactans, beta glucan, dextrans,fructooligosaccharides, fucosyllactose, galactooligosaccharides,galactomannans, gentiooligosaccharides, glucooligosaccharides, guar gum,inulin, isomaltooligosaccharides, lactoneotetraose, lactosucrose,lactulose, levan, malto dextrins, milk oligosaccharides, partiallyhydrolyzed guar gum, pecticoligosaccharides, resistant starches,retrograded starch, sialooligosaccharides, sialyllactose,soyoligosaccharides, sugar alcohols, xylooligosaccharides, theirhydrolysates, and combinations thereof.

In an embodiment, the composition includes a probiotic. The probioticmay preferably be selected from the group consisting of Aerococcus,Aspergillus, Bacteroides, Bifidobacterium, Candida, Clostridium,Debaromyces, Enterococcus, Fusobacterium, Lactobacillus, Lactococcus,Leuconostoc, Melissococcus, Micrococcus, Mucor, Oenococcus, Pediococcus,Penicillium, Peptostrepococcus, Pichia, Propionibacterium,Pseudocatenulatum, Rhizopus, Saccharomyces, Staphylococcus,Streptococcus, Torulopsis, Weissella, and combinations thereof.

In an embodiment, the composition includes an amino acid. The amino acidmay preferably be selected from the group consisting of alanine,arginine, asparagine, aspartate, citrulline, cysteine, glutamate,glutamine, glycine, histidine, hydroxyproline, hydroxyserine,hydroxytyrosine, hydroxylysine, isoleucine, leucine, lysine, methionine,phenylalanine, proline, serine, taurine, threonine, tryptophan,tyrosine, valine, and combinations thereof.

In an embodiment, the composition includes a fatty acid component,preferably a fish oil or a component thereof, which is preferablyselected from the group consisting of docosahexaenoic acid (“DHA”),eicosapentaenoic acid (“EPA”), and combinations thereof. DHA and EPA mayalso be derived from krill, plant sources containing co-3 fatty acids,flaxseed, walnut, algae, and combinations thereof. Certain fatty acids(e.g. 18:4 fatty acids) may also be readily converted to DHA and/or EPA.The composition may include a-linolenic acid.

In an embodiment, the composition includes a phytonutrient. Thephytonutrient may preferably be selected from flavonoids, alliedphenolic compounds, polyphenolic compounds, terpenoids, alkaloids,sulphur-containing compounds, and combinations thereof, and inparticular from the group consisting of carotenoids, plant sterols,quercetin, curcumin, limonin, and combinations thereof.

In an embodiment, the composition includes an antioxidant. Theantioxidant may preferably selected from the group consisting ofastaxanthin, carotenoids, coenzyme Q10 (“CoQ1O”), flavonoids,glutathione, Goji (wolfberry), hesperidin, lactowolfberry, lignan,lutein, lycopene, polyphenols, selenium, vitamin A, vitamin C, vitaminE, zeaxanthin, and combinations thereof.

It should be understood that various changes and modifications to thepresently preferred embodiments described herein will be apparent tothose skilled in the art. Such changes and modifications can be madewithout departing from the spirit and scope of the present subjectmatter and without diminishing its intended advantages. It is thereforeintended that such changes and modifications be covered by the appendedclaims.

The invention is claimed as follows:
 1. A method of treating dysphagiacomprising administering to an individual having the dysphagia acomposition comprising a therapeutically effective amount ofp-anisaldehyde.
 2. The method of claim 1, wherein the dysphagia is oralpharyngeal dysphagia.
 3. The method of claim 1, wherein the compositionis a thickened beverage.
 4. The method of claim 1, wherein thetherapeutically effective amount of p-anisaldehyde provokes a swallowingreflex.
 5. The method of claim 1, wherein the p-anisaldehyde is selectedfrom the group consisting of isolated p-anisaldehyde and syntheticp-anisaldehyde.